PROJECT SUMMARY Increased renal sympathetic activity is a causal pathogenetic mechanism of both cardiovascular hypertension and progressive loss of renal function in patients with chronic kidney disease (CKD). In millions of patients with resistant hypertension, dependable thermal disruption of targeted renal sympathetic nerves can reduce blood pressure and ultimately prevent heart disease, stroke and kidney failure. This has generated much excitement about the field of renal sympathetic denervation (RSDN). Currently available ablation catheters are plagued by inconsistent heating and absence of thermal feedback from the targeted treatment volume, significantly reducing RSDN benefits. Overcoming limitations of current RSDN device is thus an urgent clinical need. We propose to integrate reliable heating mechanism with real-time accurate thermal feedback into an innovative low-cost ablation device. The proposed InSite? RSDN catheter utilizes a dual?purpose microwave antenna which provides two unique advantages: i) dependable ablation zone by angularly uniform and artery-sparing targeted heating; ii) real-time dosimetry and guidance by passively collecting thermal radiation from multiple sensing volumes with an ultrasensitive radiometer. The immediate goal is to implement accurate temperature feedback in the microwave ablation catheter and test the complete system in realistic phantom and ex-vivo models. The long term objective is to dramatically improve reliability and accuracy of renal denervation by providing clinicians with precise nerve targeting and real-time thermal dosimetry. The rationale for our combined approach is that previous developments at Symple Surgical and Duke University already established suitable technology for both targeted heating and multi-frequency radiometry. Our underlying hypothesis is that by combining the best microwave technologies to ablate and monitor temperature, we improve treatment quality. Better therapy will ultimately improve clinical outcomes while maintaining safety profile. For Phase I, these are the specific aims: 1) Integrate multiband radiometric sensing into a micro-ablation catheter for continuous control during percutaneous RSDN; 2) Test the ability to accurately feedback microwave heating, in realistic phantom and ex-vivo renal tissue models. By end of Phase I, the device will be ready for subsequent animal and human studies in Phase II to correlate ablation zones with effective nerve deactivation areas. Specific milestones to prove Phase I success are: 1) Optimized integration of high sensitivity multiband radiometry in an intravascular microwave ablation catheter; 2) Algorithm to reconstruct volumetric tissue temperature across the heated zone at multiple distances from the renal artery wall; 3) Software that implements real time ablation feedback and displays precise temperature profiles; 4) Preparation of all hardware, software, procedures, and approvals for clinical investigation in Phase II. The overall expected outcome is a novel RSDN catheter with angularly-symmetric ablation and real- time thermal dosimetry. We anticipate that catheterization labs will adopt InSite? ablation catheter to accurately control size and quality of RSDN, thereby reducing death from cardiovascular disease and chronic kidney failure.